Hormone replacement therapy (HRT) prevents postmenopausal bone loss and fractures. However, the occurrence of women with no bone response to HRT has not been widely examined. We identified the densitometric nonresponders to long-term HRT and investigated some characteristics and biochemical variables as possible predictors of densitometric nonresponse in postmenopausal women. The study population was a subsample of the Kuopio Osteoporosis Study (n = 14,220). A total of 464 early postmenopausal women were randomized into four treatment groups: (1) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate); (2) vitamin D3; (3) HRT + Vitamin D3 combined; and (4) placebo. In this study, the data from HRT and placebo groups were analyzed. Lumbar (L2-4) and femoral neck bone mineral density (BMD) were determined by dual-energy X-ray absorptiometry (DXA) at baseline and after 5 years of treatment. A densitometric nonresponder was defined as a woman whose 5-year BMD change was similar to the mean BMD change (+95% CI) of the placebo group or worse. Altogether, 74 women in the HRT group and 104 women in the placebo group complied with the treatment. According to spinal BMD analysis, 11% of the women were classified as densitometric nonresponders; the corresponding proportion for femoral BMD analysis was 26%. Both smoking (p = 0.003) and low body weight (p = 0.028) were significant risk factors for densitometric nonresponse to HRT. After 6 months of treatment the densitometric nonresponders (hip) had a significantly higher mean serum follicle stimulating hormone (FSH) level (p = 0.038) and lower increases in serum estradiol levels (p = 0.006) than the densitometric responders. The mean changes in serum FSH and alkaline phosphatase levels were significantly lower among the densitometric nonresponders (spine) than responders (p = 0.043 and 0.017, respectively). In conclusion, this prospective study shows that especially current smokers and women with low body weight are at increased risk of poor bone response to HRT. Repeated serum FSH, estradiol and alkaline phosphatase measurements during the first months of long-term HRT may be helpful in identifying the women with no bone response to HRT.

In this study, cefuroxime appeared to be effective in prophylaxis against infections. Metronidazole appeared to be ineffective, with no additional risk-reductive effect when combined with cefuroxime.

The effects of vitamin D (VitD) and estrogen therapy (HRT) on bone mineral density (BMD) were studied in postmenopausal women in a 2.5 year follow-up. The study population was a subgroup of the Kuopio Osteoporosis Study(n=13100). 464 women (mean age 52.7• mean duration of menopause 1.1• yr) were randomized into 4 groups: I.HRT; a sequential combination: 2mg E 2 valerate and img cyproterone acetate (E2V/CPA) (=Climen R) n=83; 2.VitD(cholecalsiferol 3001U/day;not June-August) n=104; 3. E;V/CPA +VitD n=92; 4. Calcium lactate (93mg Ca 2.) as a placebo n=109. Spinal (L2-4) and femoral neck BMD were determined by dual X-ray absorptiometry (DXA) before and after 2.5 years' treatment. Student's T-test for paired data was used. The groups were statistically equal at the baseline.After 2.5 years, lumbar BMD had increased by 1.7% in the E2V/CPA (p=0.000) and by 1.3% in the E2V/CPA +VitD group (p=0.002), Lumbar BMD decreased by -3.5% in the VitD (p=0.000) and by -3.7% in the placebo group (p=0.000). Femoral BMD decreased by -2.5% in the VitD (p=0.000) and by -3.7% in the placebo group (p=0.000) but, the decrease was non-significant in the E2V/CPA and E2V/CPA +VitD groups.Our results confirm the beneficial effect of HRT On spinal BMD. Vitamin D appears to be ineffective in prevention of osteoporosis in postmenopausal women and HRT and vitamin D is not more effective than HRT alone.Several attempts have been undertaken in the past, to design antagonists of PTH and PTHrP. Here we describe a novel type of antagonists based on position-10-modified analogues of hPTHrP. /n vitro, SDZ 161 (Naphthyl(2)-acetyl-[3-naphthyl(2)-alanine1~ SDZ 162 (Naphthyl(2)acetyl-[3-naphthyl(2)-alaninet~ )-NHs) and SDZ 219 (Succinyl-[phes, naphthyl(2)-alanine~~ inhibited binding of [r~I-Tyr'~JchPTHrP-(1-36)-NH2 in OK-1 cells with pKo values of 8.3, 7.9 and 8.4, respectively. The analogues were devoid of intrinsic activity on adenylate cyclase in vitro. They were full competitive antagonists versus hPTH-(1-34)-stimulated cAMP production in UMR-t 06-06 cells with pA~ values of 10.3, 9.7, and 9.3, respectively. In vivo, infusion of the antagonists alone (45 nmolkg 4 h -1) for 4 h had no effect on urinary phosphate (Pi) and cAMP excretion nor on plasma calcium levels in TPTX rats. When hPTH-1 1 (1-34) (0.9 nmol kg h, for 4 h) and the respective antagonist (45 nmol kg 1 h -1 for 5 h, starting 1 h before the agonist) were infused i.v., SDZ 161 and SDZ 219 blocked PTH mediated increases of Pj and cAMP completely for about 2 h, thereafter only partially. Under the same experimental conditions, rryr~]bPTH-(7-34)-NH=, which had been described as a potent PTH antagonist in vivo (Hoduchi N et el. (1983), Science, 220:1053-1055"), or SDZ 162 showed only minimal inhibition of PTH-mediated responses. Conclusion: SDZ 161 and SDZ 219 are very potent PTH antagonists in vitro. In vivo, they are devoid of intrinsic activity and able to inhibit PTH-mediated effects in the kidney. Although being considerably more potent as antagonists than [Tyr~bPTH-(7-34)-NH=, they failed ...

PURPOSE= To quantify the loss of BDM after HRT with two doses of tibolone 1.25 mg/d(A) (nffi25) and 2.5 mg/d(B) (n=23) as compared to placebo(C) (nffil6). METHODS= 94 postmenopausal women, participated in a 2 year randomized, placebo controlled study to evaluate the effect of tibolone on trabecular and cortical BMD. 64 volunteered for an assessment of BMD one year after completing the study. Trabecular BMD of the spinewas measured with Quantitative Computed Tomography, cortical BMD was estimated by Quantitative Microdensitometry of the mid-phalanx. Change of BMDwas expressed as the mean percent change from baseline. RESULTS= During the study trabecular EMD changed in group A, B and C (3.2%, 9.3% and -6.7%, resp.). Loss of trabeeular BMD in the post-trial year for group A, B and c was -7.0%, -12.1% and -2.6%, resp. This loss was significantly different between all groups (p<0.001}. During the study cortical BMD changed in group A, B and C (4.6%, 5.5% and -1.4%, resp.). Loss of cortical END in the post-trial year for group A, B and C was -2.6%, ,2.4% and -2.4%, resp., which was not significantly different from each ether. 9ONCLUBION= In contrast to cortical BMD, there is an increased loss of trabecular BMD in the first year after HRTwith tibolone. These data suggest that long-term HRT with tibolone is needed for prevention of osteoporosis, similar to estrogens.